Moment Analysis of Drug Disposition in Kidney.III: Transport of p-Aminohippurate and Tetraethylammonium in the Perfused Kidney Isolated from Uranyl Nitrate-Induced Acute Renal Failure Rats

Abstract

A different manner of insufficiency of renal epithelial cell transport between the organic anion and cation, p-aminohippurate and tetraethylammonium, respectively, was observed in the perfused kidney isolated from uranyl nitrate-induced acute renal failure (ARF) rats.The single-pass outflow pattern of the perfused kidney was analyzed by noncompartmental moment analysis. The active tubular secretion was impaired faster than the reduction of glomerular filtration, and the tetraethylammonium secretion decreased at an earlier stage of ARF than p-aminohippurate. The apparent uptake rate constant from blood to cells of p-aminohippurate was reduced with the progress of ARF and associated with the amount of this drug secreted, whereas the uptake rate constant of tetraethylammonium did not change until the late stage of ARF. The mean residence time in renal epithelial cells of tetraethylammonium was prolonged with reduction of the amount to be secreted, while that of p-aminohippurate remained unchanged. Therefore, the uptake of p-aminohippurate across the basolateral membranes decreased gradually, and the transport across the brush border membranes was still unchanged after uranyl nitrate treatment. On the other hand, the secretion of tetraethylammonium from cells to lumen was impaired at first, and then the uptake from blood to cells was impaired.These results suggest that impairment by uranyl nitrate-induced ARF appears at the carrier-mediated transport process of the epithelial cell membranes for both organic anions and cations.